Huang D, Shi F D, Giscombe R, Zhou Y, Ljunggren H G, Lefvert A K
Department of Neurosciences NC30, The Lerner ResearchInstitute, Cleveland Clinic Foundation, 9500-10000 Euclid Avenue, Cleveland, OH 44195, USA.
Eur J Immunol. 2001 Jan;31(1):225-32. doi: 10.1002/1521-4141(200101)31:1<225::AID-IMMU225>3.0.CO;2-0.
Human autoimmune myasthenia gravis (MG) is associated with the IL-1beta TaqI RFLP allele 2. Individuals positive for this allele have high levels of inducible IL-1beta in their peripheral blood. Here, we have characterized MG induction and the immune response elicited by Torpedo acetylcholine receptor (AChR) immunization in wild-type and IL-1beta deficient (-/-) mice. Compared with wild-type mice, IL-1beta-/- mice were relatively resistant to induction of clinical experimental autoimmune myasthenia gravis (EAMG). Draining lymph node cells from IL-1beta-/- mice showed poor proliferative capacity upon AChR stimulation in vitro. Both Th1 (IFN-gamma, IL-2) and Th2 (IL-4) cytokine responses were reduced and levels of serum anti-AChR antibodies decreased in IL-1beta-/- mice compared to wild-type mice. Taken together, these results reveal a critical role for IL-1beta in the induction of MG in mice, and support a role for IL-1beta in the pathogenesis of MG in man.
人类自身免疫性重症肌无力（MG）与白细胞介素-1β TaqI 限制性片段长度多态性（RFLP）等位基因2相关。携带该等位基因的个体外周血中可诱导的白细胞介素-1β水平较高。在此，我们对野生型和白细胞介素-1β缺陷型（-/-）小鼠中由电鳐乙酰胆碱受体（AChR）免疫引发的MG诱导及免疫反应进行了特征描述。与野生型小鼠相比，白细胞介素-1β基因敲除小鼠对临床实验性自身免疫性重症肌无力（EAMG）的诱导相对具有抗性。来自白细胞介素-1β基因敲除小鼠的引流淋巴结细胞在体外经AChR刺激后增殖能力较差。与野生型小鼠相比，白细胞介素-1β基因敲除小鼠中Th1（干扰素-γ、白细胞介素-2）和Th2（白细胞介素-4）细胞因子反应均降低，血清抗AChR抗体水平也降低。综上所述，这些结果揭示了白细胞介素-1β在小鼠MG诱导中的关键作用，并支持白细胞介素-1β在人类MG发病机制中的作用。
